Elsevier

Pharmacology & Therapeutics

Volume 200, August 2019, Pages 135-147
Pharmacology & Therapeutics

Consideration of breast cancer subtype in targeting the androgen receptor

https://doi.org/10.1016/j.pharmthera.2019.05.005Get rights and content
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open access

Abstract

The androgen receptor (AR) is a drug target in breast cancer, and AR-targeted therapies have induced tumor responses in breast cancer patients. In this review, we summarized the role of AR in breast cancer based on preclinical and clinical data. Response to AR-targeted therapies in unselected breast cancer populations is relatively low. Preclinical and clinical data show that AR antagonists might have a role in estrogen receptor (ER)-negative/AR-positive tumors. The prognostic value of AR for patients remains uncertain due to the use of various antibodies and cut-off values for immunohistochemical assessment. To get more insight into the role of AR in breast cancer, we additionally performed a retrospective pooled analysis to determine the prognostic value of the AR using mRNA profiles of 7270 primary breast tumors. Our analysis shows that a higher AR mRNA level is associated with improved disease outcome in patients with ER-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors, but with worse disease outcome in HER2-positive subgroups. In conclusion, next to AR expression, incorporation of additional tumor characteristics will potentially make AR targeting a more valuable therapeutic strategy in breast cancer.

Keywords

Breast cancer
Androgen receptor
AR antagonist
Estrogen receptor
Human epidermal growth factor receptor 2
Triple-negative breast cancer

Abbreviations

AR
androgen receptor
CBR
clinical benefit rate
CI
confidence interval
DFS
disease-free survival
DHT
dihydrotestosterone
ER
estrogen receptor
HR
hazard ratio
HER2
human epidermal growth factor receptor 2
HER3
human epidermal growth factor receptor 3
HR
hormone receptor
IHC
immunohistochemistry
LAR
luminal androgen receptor
LHRH
luteinizing hormone-releasing hormone
NA
not available
OS
overall survival
PFS
progression-free survival
PR
progesterone receptor
TNBC
triple-negative breast cancer
Wnt
Wingless protein

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